Sachets for bio-pharmaceutical fluid products

ABSTRACT

A flexible sachet for transporting bio-pharmaceutical liquids with a volume of 50 liters or more, of the bellows type, assumes when filled a substantially parallelepiped shape. It comprises a bottom wall, a top wall and four lateral walls. It is made of a single laminated film with three or more layers, the innermost layer being a plastics material layer that can be heat welded and is biocompatible with the media transported. A method of manufacturing the sachet is also disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention concerns new flexible sachets for transportingbio-pharmaceutical fluid products and a method of manufacturing them.

2. Description of the Prior Art

U.S. Pat. No. 5,350,080 describes sachets which can be used for cellularculture media and their rigid transportation container.

The bio-pharmaceuticals industry, understood in the broadest sense, isincreasingly using flexible sachets with capacities in the range 20liters to 2 000 liters and more, in particular bio-compatible sachets,to transport fluids use in the industry, such as culture media, cellularcultures, buffer solutions, artificial nutrient liquids, blood productsor derived products such as plasma.

Sometimes the products contained in such sachets are used thousands ofkilometers from the place where the sachets were filled. These productsare often extremely valuable in financial terms and often extremelyvaluable in terms of the health of persons because they can be used tomanufacture medication for human use, for example. It is thereforeessential for such sachets to reach their destination safely, filledwith the liquid with which they were initially filled, and free ofcontamination.

Flexible sachets of the above kind are subject to many kinds of stressduring transportation: acceleration, braking, tossing, shaking,vibration, etc and therefore to many forces including shear forces whichtend to deteriorate the film from which they are made, especially atsensitive locations such as folds. Consequently these various stressesfrequently lead to weakening, rupture or piercing of the sachets.

It must be remembered that sachets of the above kind intended to containthe previously mentioned liquid products and media are by their verynature provided with a number of access ports enabling their content tobe filled, drawn off, mixed, etc, for example, and usually with a numberof tubes installed at some or all of these access ports. The tubes arethemselves often fitted with one or more rigid material devices such asvalves, filters or clamps which can contribute to abrasion of the upperpart of the sachets when they are transported over long distances. Ahole in the top of a sachet can be just as serious as one elsewhere, forexample in the situation of transporting sterile contents.

This is why it would therefore be desirable to have a sachet fortransporting bio-pharmaceutical liquids with a volume of 50 liters ormore which in addition to the usual qualities of such sachets, i.e.biocompatibility, sterilizability, impermeability to gases and inparticular to oxygen, would be particularly resistant to transportationover long distances and easy to manufacture.

Sachets for transporting bio-pharmaceutical liquids in the form ofbellows with walls constructed by manually welding three separateindependent films are known in themselves.

Sachets of the above type are sold by HyClone Laboratories, for example.They have capacities in the range 1 liter to 1 000 liters, for example.However, when transported over long distances, given the many stressesto which the sachets are subjected, a number of them are lost because ofleaks.

This is why the subject matter of the present application is a flexiblesachet for transporting bio-pharmaceutical liquids with a volume of 50liters or more, of the bellows type, assuming when filled asubstantially parallelepiped shape, comprising a bottom wall, a top walland four lateral walls, which is made of a single laminated film withthree or more layers, and preferably made of four pieces of the saidsingle laminated film, the innermost layer being a plastics materiallayer that can be heat welded and is biocompatible with the mediatransported.

The bio-pharmaceutical liquids transported can be culture media, cellcultures, buffer solutions, artificial nutrient liquids, blood productsor derivatives such as plasma, for example.

The sachet of the invention is a bellows type sachet, i.e. one in which,when laid flat, two opposite sides of the sachet are folded inwards.

The expression "laminated single film" or "monofilm" means that the filmfrom which the walls of the sachet are made appears to be a single filmalthough in fact it is made from a plurality of layers of films ofdifferent kinds stuck together.

In accordance with the invention, the laminated single film comprises atleast three layers and preferably four layers.

The inside layer is a layer of plastics material that can be heat weldedand is biocompatible with the media transported. These plasticsmaterials include polyolefins, for example, and preferably polyethylene(PE), especially low-density and in particular ultra-low-densitypolyethylene.

The thickness of this layer can be in the range 50 μm to 200 μm, forexample, and in particular in the range 100 μm to 200 μm.

The intermediate layer constituting a barrier to gases such as oxygen,carbon dioxide or water vapor, is for example made of polyamide (nylon)6, polyamide 8, polyamide 11, polyamide 12, polyamide 6--6, polyamide6-10, polyamide -6 or polyamide 6/polyamide 6--6 copolymers. Mixtures ofgas barrier polymer resins can also be used such as a mixture ofpolyamide or polyethylene and ethylene/vinyl alcohol copolymer (EVOH) inpolyvinylidene chloride (PVDC). A plastics material that has beensurface treated with aluminum oxide or silica can equally be used. Underpreferred conditions of implementation, the gas barrier intermediatelayer is made of an ethylene/vinyl alcohol copolymer.

The thickness of this layer can be in the range 6 μm to 20 μm, forexample, and in particular in the range from 10 μm to 20 μm.

The external layer is preferably made from a plastics material that hasan insulating effect vis a vis heat welding, for example polyolafin orpolyamide resin and preferably polyester (PET) resin.

The thickness of this layer can be in the range 10 μm to 30 μm, forexample, and in particular in the range 10 μm to 20 μm.

Under preferred conditions of implementation of the invention thelaminated film includes a fourth layer which is advantageously betweenthe external layer and the gas barrier intermediate layer, improving themechanical strength of the laminated single film.

This second intermediate layer can be of polyolafin or PET, for example,and is preferably of polyamide, advantageously polyamide 6.

The adhesive used to attach the various layers together is preferablyone of the adhesives conventionally used in the field of laminatedpolymer films. An epoxy adhesive is preferably used, in particular oneof the polyurethane-polyester type.

The above polymers can be mixed with additives. For example, thepolyethylene of the inner layer can have a slippery agent added to itsuch as erucylamide in a concentration of 600 ppm and/or a silicon oxideat a concentration of 2 000 ppm.

Under preferred conditions of implementation of the invention, the abovesachet is made from four pieces of film by flat heat welding.

This parallelepiped shape can in particular be obtained by cutting theedges of the film at 30° to 60° and approximately 45° relative to thevertical axis of the sachet.

By definition, the "bottom face" and the "top face" of the sachet arethe faces of the sachet such that the welds cross over on these facesbut are parallel to each other on the "lateral" faces of the sachet.

Under other preferred conditions of implementation of the invention, theabove sachet has on its top face a preferably elongate flange formounting connectors comprising one or more chimneys for fittingconnectors which are preferably identical, and in particular aligned,comprising two substantially cylindrical concentric lips.

These chimneys can advantageously cooperate with connectors having acylindrical end sized to be inserted between the lips of the chimney.Their number is preferably in the range 1 to 8, in particular 2 to 6,especially 3 to 5.

Under preferred conditions of implementation the connectors furthercomprise an outer skirt surrounding the outer lip of the access chimney.

The connectors can have any conventional configuration such as, forexample, fittings for tubes such as, for example, fittings for small,medium or large diameter tubes, stoppers, right-angle connections, andthese connectors, in particular those for right-angle connections, canthemselves comprise a double-lip system similar to that of the chimneysfor connectors, for example.

Under other preferred conditions of implementation of the invention theflange for mounting connectors is made of polyolefin resin andpreferably of an ethylenevinyl acetate copolymer.

Under other preferred conditions of implementation of the invention theconnectors are glued to the chimneys using a solvent or non-solventglue.

The present invention also consists in a sachet of the above kind fittedwith connectors installed on the above chimneys.

Under other preferred conditions of implementation of the invention allthe materials used to construct the sachet of the invention and itsaccessories are capable of withstanding exposure to radiation and otherknown sterilization techniques.

Under other preferred conditions of implementation of the invention theflange for mounting connectors carrying the chimneys is heat welded tothe sachets.

Under other preferred conditions of implementation of the invention themounting flange has in its lower part, opposite the access chimneys, oneor in particular several spaced protuberances constituting passages, forexample semi-toroidal passages, which prevent the plate being pressedtotally against the bottom of the sachet when it is emptied.

Under further preferred conditions of implementation of the inventionthe mounting flange has standardized chimneys enabling easycustomization of the outlet accessories and valves (stopper, angled orstraight outlet, variety of diameters, etc).

Under other preferred conditions of implementation of the invention thebottom face of the sachet is fitted with a bung, for example anevacuation or filling bung. The evacuation or filling bung can bemounted on the sachet in the same way as the above plate. Underpreferred conditions of implementation of the invention the bungincludes a 90° outlet.

Under further preferred conditions of use of the invention the emptyingbung is mounted on a base installed in such a manner that it projectsoutwardly of the bottom of the sachet. The projecting part of the bungis preferably of polygonal shape or of any other non-circular shape,such as elongate oval, triangular, square, hexagonal, etc. Thisparticular shape allows good centering of the sachet when the latter isinstalled in a rigid container for transportation by cooperation with anorifice of complementary shape and corresponding located on the bottomof the container. Also, the corners of the sachet can fit closely intothe corners of the container without risk of twisting of the sachet. Thebung can at the same time constitute a point at which the sachet isanchored to the bottom of the container, which improves transport.

Under other preferred conditions of implementation, the pro-eminent baseof the bung has a peripheral groove which can cooperate with a clip sothat it can be clipped when it is fitted into the container for filling.In this way the original position of the sachet is preserved.

The present invention also consists in a method of manufacturing asachet as defined hereinabove wherein a top film, a bottom film and twolateral films folded on themselves are paid out in such a manner as tobring the heat weldable plastics material layers into contact with eachother and in a flat configuration, leaving a gap between the two lateralfilms, followed by heat welding of the sides two by two and of the topand bottom of the sachet.

Under preferred conditions of implementation of the invention the topand bottom welds of the sachet are K-welds, the branches of the K beinginclined at approximately 45° to the direction of movement of the piecesof multilayer monofilm, for example in the range 30° to 60°, as in theexamples hereinafter.

Under preferred conditions of implementation of the invention the heatwelding is effected using heating bars. A single weld can be effected ata given location. However, one, two or in particular three successivewelds are preferably effected. In the case of welds in a plurality ofsteps, the steps are preferably effected at different temperatures.

Under other preferred conditions of implementation of the invention thewelds are effected with a width in the range 5 mm to 20 mm, preferably 5mm to 15 mm and in particular 8 mm to 15 mm.

The other operations, such as cutting the films at the welds, areconventional.

It is therefore possible to proceed in a single step to a plurality ofwelding operations at the same level, given the presence of the externallayer which has an insulating effect vis a vis heat welding. Thus onlythe internal layer are welded together.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in more detail with reference to theaccompanying drawings, in which:

FIG. 1 is a perspective view of a sachet in accordance with theinvention in the configuration that it assumes when filled, beforefitting a bung and a connector mounting flange.

FIG. 2 represents a top view of a sachet when flat before fitting a bungand a connector mounting flange.

FIG. 3 represents a perspective view of the placement of four films andtwo longitudinal heating bars (for welding one side of a sachet) duringthe manufacture of a sachet.

FIG. 4 represents a front view of the films and of two transverseheating bars (for welding the top and the bottom of a sachet) during themanufacture of a sachet.

FIG. 5 represents a top view of the location of the top or bottom weldsof a sachet.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS EXAMPLE 1

Fabrication of a four-layer film

A laminated film with the following structure is made by gluing:

    ______________________________________                                        Resin                    Thickness                                            ______________________________________                                        PET                      12 μm                                             Polyurethane-polyester epoxy adhesive                                                                  2.5 μm                                            PA6                      15 μm                                             Polyurethane-polyester epoxy adhesive                                                                  2.5 μm                                            EVOH                     12 μm                                             Polyurethane-polyester epoxy adhesive                                                                  2.5 μm                                            Ultra-low density PE     150 μm                                            ______________________________________                                    

EXAMPLE 2

Fabrication of a sachet

On an automatic machine designed for this purpose, four spools ofplastics material film from example 1 are paid out to constitute thefour walls of a cubic or parallelepiped-shape sachet: two films arestretched flat (top and bottom) and two films are conformed as flatbellows and inserted between the first two.

The four longitudinal welds are executed by effecting three 30 cm to 90cm longitudinal weld sections in succession in accordance with apredetermined advance movement of the film. Each of the three welds iseffected at a different temperature.

This method guarantees

the strength of the welds, and

minimum overlap between the welded film sections and the welding bars sothat the height of the sachet can be varied.

The sachet top and bottom welds are effected one after the other by thesame method and with a minimum of one weld and preferably with threesuccessive welds at different temperatures.

The sachet top and bottom welds are effected by a set of welding barssituated:

on the one hand, at 90° to the advance movement of the film, enablingwelding of a section comprising 4+2+4 thicknesses of film ("transverse"weld,) and

on the other hand, at an angle in the range 30° to 60° relative to theadvance movement of the film in order for the sachet deployed in threedimensions to conform exactly to the geometry of the bottom and thesides of a rigid container in which it will be placed ("K" weld).

The above transverse and K welds are effected at the exact intersectionof the two films of the bellows with the two flat films. This ensuresthat the sachet is sealed and strong.

Between the operations of effecting the top and bottom sachet welds(transverse and K welds) the following three complementary operationsare effected to impart to the sachet the required features for fillingand emptying from the top and from the bottom:

1) die-cutting the flat top and/or bottom film,

2) installing a flange for connectors and/or a bung,

3) heat welding the flat film(s) to the connector and/or bung(s).

FIG. 1 shows a flexible sachet 1 in accordance with the inventioncomprising a bottom wall 2, a top wall 3 and four side walls. The bottomwall 2 is fitted with a bung 4 for draining off the bio-pharmaceuticalliquid that it contains. The bung has an upstanding base 5, here ofhexagonal shape, which can cooperate with an orifice of complementaryshape in the bottom of a rigid container for transporting sachets. Thebase has a groove 6 for fitting a clip to immobilize the bung relativeto the container, sandwiched between the bung base mounting flange andthe clip.

A flange 7 for fitting connectors is fitted to the top face 3 of thecontainer 1 (here it is shown separately from the sachet). The flangehas four identical chimneys 8 each formed by two concentric lips. Theend of each chimney inside the sachet includes four spaced semi-toroidalprotuberances 9 with a gap between two successive protuberances 9.Connectors 10, 11, 12, 13 can be installed on these chimneys and herethey are respectively connectors for large diameter tubes, for smalldiameter tubes, a stopper and a 90° elbow itself incorporating a chimneyof similar construction to the previous ones and to which anotherconnector 15 can be fitted, here of similar structure to the connector10 for large diameter tubes.

This figure also shows the structure of the welds on the top and bottomface, firstly a weld 16 transverse to the advance movement of the filmsduring fabrication of the sachet and welds inclined to this axis, welds17 and 17' on the one hand (effected simultaneously) and welds 18 and18' (also effected simultaneously). The lateral welds 19 and 19' arealso effected simultaneously and likewise the welds parallel to them onthe opposite face.

Finally, note an orifice 14 on the top wall 3 of the sachet for mountingthe flange 7. The bottom wall 2 of the sachet also has an orifice forfitting the bung 4.

FIG. 2 shows the same components as FIG. 1 except that the sachet isflat, as immediately after fabrication. Accordingly the welds 17 and 17'can be seen to be superposed and likewise the welds 18, 18' and 19, 19'.

In this figure the flange 7 and the bung 4 are shown enlarged relativeto the sachet 1. It can also be seen that in the central part of thesachet, where the orifices for the flange and the connector can be seen,there are only two thicknesses of laminated film, whereas at the sidesthere are four thicknesses of film.

FIG. 3, which illustrates the manufacture of a sachet in accordance withthe invention, shows how the films are paid out. Two films 20 and 21 aretensioned flat, one at the top and one at the bottom, and two films 22and 23 are conformed into flat bellows and inserted folded between thefirst two films. Two heating bars 24 and 25 sandwich the fourthicknesses of film from the three different films 20, 21, 23 to producetwo welds simultaneously. Similarly on the opposite side (the heatingbars on the opposite side are not shown).

FIG. 4 shows the bars 26 and 27 which make the transverse welds at thetop and bottom of the sachet (shown at 16 in FIGS. 1 and 2).

As mentioned above, it can be seen that using this manufacturingtechnique there are two areas 28 and 29 in which there are fourthicknesses of film constituting the sachet whereas in an intermediatearea 30 there are only two thicknesses. Nevertheless, given theparticular structure of the films in accordance with the invention, flatfabrication produces welds and sachets of great strength, even duringtransportation over long distances.

FIG. 5 shows the principle of the "K" weld comprising, on the one hand,a weld perpendicular to the advance movement of the films, as shown inFIG. 4, and producing the weld 16, and two inclined welds 31 and 32corresponding to those shown at 17, 17' and 18, 18' in FIGS. 1 and 2.

When the welding operations have been completed, the external parts ofthe films can obviously be cut off beyond the welded areas.

There is claimed:
 1. A flexible sachet for transportingbio-pharmaceutical liquids with a volume of 50 liters or more, of thebellows type, assuming when filled a substantially parallelpiped shape,comprising a bottom wall, a top wall and four lateral walls, which ismade of a single laminated film with three or more layers, the innermostlayer being a plastics material layer that can be heat welded and isbiocompatible with the media transported, and a flange on its top facefor mounting connectors comprising one or more chimneys for fittingconnectors, said chimneys comprising two substantially cylindricalconcentric lips.
 2. The flexible sachet claimed in claim 1 made fromfour pieces of said laminated single film.
 3. The flexible sachetclaimed in claim 1 wherein said laminated single film comprises fourlayers.
 4. The flexible sachet claimed in claim 1 wherein an innermostlayer is of polyethylene and its thickness is in the range 50 μm to 200μm.
 5. The flexible sachet claimed in claim 1 wherein an intermediatelayer is a barrier to gases, such as oxygen, carbon dioxide and watervapor, and is made of ethylene/vinyl alcohol copolymer and its thicknessis in the range 6 μm to 20 μm.
 6. The flexible sachet claimed in claim 1wherein an outermost layer is made of polyester (PET) and its thicknessis in the range 6 μm to 20 μm.
 7. The flexible sachet claimed in claim 1comprising a fourth layer increasing the mechanical strength of saidlaminated single film.
 8. The flexible sachet claimed in claim 7 whereina second intermediate layer is made of polyamide.
 9. The flexible sachetclaimed in claim 1 fabricated by heat welding flat from four pieces offilm.
 10. The flexible sachet claimed in claim 1 fitted with connectorsinstalled on said chimneys.
 11. The flexible sachet claimed in claim 1wherein the bottom face of said sachet is fitted with a drain bung. 12.A flexible sachet for transporting bio-pharmaceutical liquids with avolume of 50 liters or more, of the bellows type, assuming when filled asubstantially parallelpiped shape, comprising a bottom wall, a top walland four lateral walls, which is made of a single laminated film withthree or more layers, the innermost layer being a plastics materiallayer that can be heat welded and is biocompatible with the mediatransported, the bottom face of said sachet being fitted with drain bungmounted on an outwardly upstanding base on the bottom of said sachet,the upstanding part of said bung having a non-circular shape.
 13. Theflexible sachet of claim 12, wherein the upstanding part of said bunghas a polygonal shape.
 14. The flexible sachet claimed in claim 12 madefrom four pieces of said laminated single film.
 15. The flexible sachetclaimed in claim 12, wherein said laminated single film comprises fourlayers.
 16. The flexible sachet claimed in claim 12, wherein aninnermost layer is of polyethylene and its thickness is in the range of50 μm to 200 μm.
 17. The flexible sachet claimed in claim 12, wherein anintermediate layer is a barrier to gases, such as oxygen, carbon dioxideand water vapor, and is made of ethylene/vinyl alcohol copolymer and itsthickness is in the range of 6 μm to 20 μm.
 18. The flexible sachetclaimed in claim 12, wherein the outermost layer is made of polyester(PET) and its thickness is in the range 6 μm to 20 μm.
 19. The flexiblesachet claimed in claim 12, comprising a fourth layer increasing themechanical strength of said laminated single film.
 20. The flexiblesachet claimed in claim 19, wherein a second intermediate layer is madeof polyamide.